This phase II trial study has a 6-patient feasibility portion studying the tolerability of chemotherapy with vincristine sulfate together with topotecan hydrochloride, cyclophosphamide, and bevacizumab in treating young patients with refractory or first recurrent extracranial Ewing's sarcoma. If the therapy is considered tolerable, this feasibility run-in will be followed by a randomized phase II portion studying giving vincristine sulfate together with topotecan hydrochloride, and cyclophosphamide to see how well it works compared with giving vincristine sulfate together with topotecan hydrochloride, cyclophosphamide, and bevacizumab in treating young patients with refractory or first recurrent extracranial Ewing's sarcoma. Drugs used in chemotherapy, such as vincristine sulfate, topotecan hydrochloride, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop tumor growth by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

Time to Disease Progression in Patients Receiving VTC With or Without Bevacizumab [ Time Frame: Maximum of 5 years after enrollment ] [ Designated as safety issue: No ]

Time from enrollment to disease progression, death, second malignant neoplasm, or last patient follow-up whichever occurs first. Patients who experience disease progression, death or second malignant neoplasm will be considered to have experienced an event; otherwise the patient will be considered censored at last follow-up.

Patients receive bevacizumab IV over 30-90 minutes on day 1, vincristine sulfate IV on days 1, 8, and 15, and topotecan hydrochloride IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-5. Treatment repeats every 21 days (except during weeks 14, 15 [course 5], 17, 18 [course 6], 26, 27 [course 9], 29, and 30 [course 10] when no chemotherapy is given) for up to 12 courses in the absence of disease progression or unacceptable toxicity.

I. To determine the feasibility of administering bevacizumab in combination with vincristine (vincristine sulfate), topotecan hydrochloride, and cyclophosphamide (VTC) to younger patients with refractory or first recurrent Ewing sarcoma.

II. To compare the progression-free survival of patients treated with VTC with bevacizumab vs VTC without bevacizumab.

SECONDARY OBJECTIVES:

I. To estimate the response rate to 2 cycles of VTC compared to 2 cycles of VTC/bevacizumab.

OUTLINE: This is a single therapy feasibility study followed by a randomized controlled portion. Patients are stratified according to time to disease recurrence (< 2 years vs >= 2 years).

ARM I (Feasibility assessment of VTCB): Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1, vincristine sulfate IV on days 1, 8, and 15, and topotecan hydrochloride IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-5. Treatment repeats every 21 days (except during weeks 14, 15 [course 5], 17, 18 [course 6], 26, 27 [course 9], 29, and 30 [course 10] when no chemotherapy is given) for up to 12 courses in the absence of disease progression or unacceptable toxicity.

At least 2 weeks since prior local palliative radiotherapy (e.g., small port)

Diagnosis of extracranial Ewing sarcoma or primitive neuroectodermal tumor of bone or soft tissue meeting 1 of the following criteria: I) a first recurrence of localized disease; II) a first recurrence of initially metastatic disease; III) disease refractory to initial conventional therapy

Patients must have RECIST-measurable disease documented by clinical, radiographic, or histological criteria

Patients who do not have measurable disease (e.g., bone scan-determined metastatic disease only) remain eligible for the study and will be evaluable for disease-free progression

Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (=< 16 years of age )

Life expectancy >= 8 weeks

Absolute neutrophil count >= 1,000/μL

NOTE: Patients with tumor metastatic to bone marrow are permitted to receive transfusions to maintain hemoglobin and platelet counts. These patients will not be evaluable for hematologic toxicity. Patients who are refractory to platelet infusions (i.e., unable to maintain platelet counts > 75,000/μL) and have marrow involvement and platelet counts < 75,000/μL are not eligible

Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy

At least 1 week since prior therapy with a biologic agent or growth factor

Patients must have histological verification of the malignancy at original diagnosis

Histological confirmation of relapse is highly recommended but not mandatory

Prior initial therapy with topotecan hydrochloride is allowed as long as > 2 years have elapsed since the initial diagnosis of Ewing sarcoma

Radiotherapy for local metastatic tumor control allowed after the first 2 courses of therapy

Other cancer chemotherapy or immunomodulating agents

Steroid use is allowed

Prior allogeneic SCT

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00516295